Backgrounds: A successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for either single or multiple lesions in the STEMI setting at the time of presentation may afford an immediate benefit. However, detailed early and mid term clinical outcomes of these two different subsets are not well known yet. Method: A total of 2572 patients (pts, male 74.1%, mean age 62짹12.8 years) presented with acute STEMI and underwent primary or early PCI (Primary or Early) with DES. Enrolled pts were divided into two groups; single lesion group (n=1247 pts) or multiple lesion group (two or more lesions; n=1325 pts) and were clinically followed for major adverse cardiac event (MACE) at 7 days and 6 months. Results: Baseline clinical characteristics were similar between the two groups. At 7 days, after multivariate analysis, the incidence of MACE in multiple lesion group was higher compared with single lesion group [59/1325 (4.5%) vs. 29/1247 (2.3%) pts, p=0.045; OR 1.638; CI 0.010-2.655]. Further, at 6 months, the incidence of MACE in multiple lesion group was significantly higher compared with single lesion group [177/1325 (13.4%) vs. 81/1247 (6.5%) pts, p < 0.001; OR 2.052; CI 1.533 – 2.748]. Conclusion: Despite the successful PCI with DES, acute STEMI pts with multiple lesion showed higher chance of MACE in 7 day and up to 6 months compared to that of pts with single lesion, suggesting more caution should be exercised for this particular subset of pts.